1.23-Hydroxybetulinic Acid Inhibits NNK and LPS-induced Lung Inflammation-related Carcinogenesis by Regulating Immune Cells in Mice
Penghaobang LIU ; Wenbin DUAN ; Yajuan CHEN ; Lanying CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):98-106
ObjectiveTo investigate the suppressive effect of 23-hydroxybetulinic acid (23-HBA), a key constituent of Pulsatillae Radix, on the pulmonary inflammation-related carcinogenesis induced by the combined exposure of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and lipopolysaccharide (LPS) in mice, alongside exploring its influence on immune cells and delving into the underlying mechanisms. MethodsA murine model of pulmonary inflammation-related carcinogenesis induced by NNK combined with LPS was established. Mice were randomly assigned into blank control, model, aspirin (10 mg·kg-1), and low-, medium-, and high-dose (3.75, 7.5, 15 mg·kg-1, respectively) 23-HBA groups. The treatment lasted for 26 weeks, after which the spleen, lung, and peripheral blood samples were collected. Lung and spleen indices were calculated. Histopathological changes in the lung tissue were observed by hematoxylin-eosin staining. Immunohistochemistry was employed to assess the expression levels of thyroid transcription factor-1 (TTF-1), neuron-specific enolase (NSE), and proliferating cell nuclear antigen (Ki-67) in the lung tissue. High-throughput protein microarray was employed to measure the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the mouse serum. Flow cytometry was employed to evaluate the expression of macrophages, myeloid-derived suppressor cells (MDSCs), and exhausted T lymphocytes in the lung and spleen tissue. Molecular docking was performed to predict the binding affinity of 23-HBA to Janus kinase 2 (JAK2), Src homology 2 domain-containing phosphatase 2 (SHP2), and suppressor of cytokine signaling 3 (SOCS3). Western blot was performed to assess the protein levels of phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), p53, and SHP2 in the M1-activated macrophages and A549 lung adenocarcinoma cells treated with 23-HBA. ResultsCompared with the normal group, the lung and spleen indexes of the model group were increased to varying degrees (P<0.05, P<0.01), the expression of TTF-1, NSE and Ki-67 protein was significantly increased (P<0.05, P<0.01), and the serum levels of TNF-α, IL-1β and IL-6 were significantly increased (P<0.01). The number of macrophages in the model group was significantly decreased (P<0.01), and the number of exhausted T cells and MDSCs was significantly increased (P<0.05, P<0.01). Compared with the model group, the spleen and thymus index of mice in each dose group of 23-HBA decreased significantly (P<0.05), and the lung index of mice in the middle dose group of 23-HBA decreased significantly (P<0.05). The high and middle dose groups of 23-HBA could improve the occurrence of inflammatory infiltration and malignant lesions in the lungs of mice induced by NNK combined with LPS in the model group. The expression of TTF-1 in the middle and high dose groups of 23-HBA was significantly lower than that in the model group (P<0.05, P<0.01). The expression of NSE and Ki-67 protein in each dose group of 23-HBA was significantly lower than that in the model group (P<0.05, P<0.01). The contents of IL-1β in the low and high dose groups of 23-HBA were significantly decreased (P<0.05), and the contents of IL-6 and TNF-α in each dose of 23-HBA were significantly decreased (P<0.05, P<0.01). The number of macrophages in the lung of the middle dose group of 23-HBA was significantly increased (P<0.05), and the number of exhausted T cells and MDSCs expressing PD-1 in the lung was significantly decreased (P<0.05, P<0.01). In addition, 23-HBA had strong molecular docking ability to SHP2, SOCS3 and JAK2 (≥7 kcal·mol-1), and significantly down-regulated the protein levels of p-STAT3, SHP2 and p53 in M1 macrophages and A549 lung adenocarcinoma (P<0.01). Conclusion23-HBA holds promise as a potential therapeutic agent for mitigating pulmonary inflammation and inhibiting malignant transformation induced by the combination of LPS and NNK. It may exert effects by regulating immune cell responses, improving the tumor immune microenvironment, and regulating key signaling pathways.
2.Identification of Dalbergia odorifera and Its Counterfeits by HS-GC-MS
Li ZHAO ; Xiaowei MENG ; Jiarong LI ; Qing ZHU ; Xianwen WEI ; Ronghua LIU ; Lanying CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):156-163
ObjectiveTo screen the differential markers by analyzing volatile components in Dalbergia odorifera and its counterfeits, in order to provide reference for authentication of D. odorifera. MethodThe volatile components in D. odorifera and its counterfeits were detected by headspace gas chromatography-mass spectrometry(HS-GC-MS), and the GC conditions were heated by procedure(the initial temperature of the column was 50 ℃, the retention time was 1 min, and then the temperature was raised to 300 ℃ at 10 ℃ for 10 min), the carrier gas was helium, and the flow rate was 1.0 mL·min-1, the split ratio was 10∶1, and the injection volume was 1 mL. The MS conditions used electron bombardment ionization(EI) with the scanning range of m/z 35-550. The compound species were identified by database matching, the relative content of each component was calculated by the peak area normalization method, and principal component analysis(PCA), orthogonal partial least squares-discrimination analysis(OPLS-DA) and cluster analysis were performed on the detection results by SIMCA 14.1 software, and the differential components of D. odorifera and its counterfeits were screened out according to the variable importance in the projection(VIP) value>2 and P<0.05. ResultA total of 26, 17, 8, 22, 24 and 7 volatile components were identified from D. odorifera, D. bariensis, D. latifolia, D. benthamii, D. pinnata and D. cochinchinensis, respectively. Among them, there were 11 unique volatile components of D. odorifera, 6 unique volatile components of D. bariensis, 3 unique volatile components of D. latifolia, 6 unique volatile components of D. benthamii, 8 unique volatile components of D. pinnata, 4 unique volatile components of D. cochinchinensis. The PCA results showed that, except for D. latifolia and D. cochinchinensis, which could not be clearly distinguished, D. odorifera and other counterfeits could be distributed in a certain area, respectively. The OPLS-DA results showed that D. odorifera and its five counterfeits were clustered into one group each, indicating significant differences in volatile components between D. odorifera and its counterfeits. Finally, a total of 31 differential markers of volatile components between D. odoriferae and its counterfeits were screened. ConclusionHS-GC-MS combined with SIMCA 14.1 software can systematically elucidate the volatile differential components between D. odorifera and its counterfeits, which is suitable for rapid identification of them.
3.Comparative Study on the Topological Attributes of Deficiency and Excess Pattern of Cerebral Small Vessel Disease Mild Cognitive Impairment Based on fMRI Graph Theory Network
Jianjun WANG ; Weimin YANG ; Haotao ZHENG ; Jianxiang CHEN ; Dongbin CAI ; Hanqing LYU ; Xiude QIN ; Lanying LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):69-75
Objective This study aimed to explore the differences in global and local brain network topological properties between deficient pattern(DP)and excess pattern(EP)of mild vascular cognitive impairment caused by subcortical small vessel disease based on graph theory network.Methods Patients were recruited prospectively and were classified with DP and EP subtype.The global small-world topological attributes and local nodes were calculated for the comparison of DP,EP,and healthy controls(CN)using the GRETNA platform.Results The three groups all had small-world attributes,but only the patients in EP had a significantly lower small world attribute δ in the range of 0.05-0.26 than the control group(P<0.05).The node efficiency and node strength indicators of multiple brain region were able to significantly distinguish the DP group from the EP group.However,there was no positive brain region in the node efficiency of the DP patients(P>0.05),and only a few brain regions showed increased node strength efficiency(P<0.05).Conclusion The results indicate that the syndrome of DP and EP have significantly different neuroimaging phenotypes,providing a basis for further research of biological classification based on Chinese Medicine syndromes.
4.Metabolomics analysis of serum and urine in patients with traumatic spinal cord injury
Jiating SONG ; Jianmin CHEN ; Kewen WANG ; Lanying HUANG ; Senming XU ; Yuchang GUI ; Jianwen XU
Chinese Journal of Tissue Engineering Research 2024;28(32):5085-5090
BACKGROUND:Traumatic spinal cord injury primarily relies on scale assessment and imaging examinations in clinical practice.However,there are limitations in predicting the prognosis of the injury.Therefore,the use of metabolomics technology for biomarker screening is significant for estimating the extent of damage,injury and recovery,as well as developing new therapies. OBJECTIVE:To characterize the metabolic features of patients with traumatic spinal cord injury using metabolomics technology and explore potential biomarkers and disrupted metabolic pathways. METHODS:Serum and urine samples were collected from 20 patients with traumatic spinal cord injury(observation group)and 10 healthy subjects(control group).Metabolites were analyzed and multivariate statistical analysis was then performed for data processing to screen differential metabolites.Metabolic pathway enrichment was performed using MetaboAnalyst software.Logistic regression was applied to construct a biomarker combination model,and its relationship with the American Spinal Injury Association grading was analyzed. RESULTS AND CONCLUSION:Significant differences in 160 and 73 metabolites were detected in the serum and urine samples of the two groups,respectively.Pathway enrichment analysis showed evident disturbances in lipid metabolism after traumatic spinal cord injury,including sphingolipid,arachidonic acid,α-linolenic acid,and arachidonic acid metabolism,as well as glycerophospholipid and inositol phosphate biosynthesis.The combination of two identified biomarkers,telmisartan and quercetin glycoside,showed a correlation with the American Spinal Injury Association grading in both serum and urine levels.Thus,metabolomics technology provides assistance in further understanding the pathological mechanisms of traumatic spinal cord injury and screening therapeutic targets.The identified metabolic biomarker combination may serve as a reference for assessing the severity of traumatic spinal cord injury.
5.Evaluation of the effect of SARS-CoV-2 infection on Doppler ultrasound and placental findings of pregnant women: a systematic review and meta-analysis
Lanying CHEN ; Tingting YIN ; Danni CAI ; Xiaomin CHEN
Ultrasonography 2024;43(6):424-437
Purpose:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect the human placenta and has been shown to have an adverse effect on Doppler ultrasound parameters and placental features. However, the specific effects of the SAS-CoV-2 infection on the fetal-placental unit in pregnant women remain unclear. The aim of this systematic review and meta-analysis was to evaluate the impact of SARS-CoV-2 infection on Doppler ultrasound and placental findings in pregnant women.
Methods:
A systematic search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. Odds ratios (ORs) were calculated, along with their 95% confidence intervals (CIs). Heterogeneity was assessed using Cochrane Q and I2 statistics and the appropriate P-value. The analysis used RevMan 5.3.
Results:
This meta-analysis included 1,210 pregnant women from 10 case-control studies. SARS-CoV-2–infected pregnant women exhibited higher likelihoods of placental abnormalities (OR, 2.62; 95% CI, 1.66 to 4.13), aberrant Doppler values (OR, 1.95; 95% CI, 1.16 to 3.27), an abnormal cerebroplacental ratio (OR, 2.68; 95% CI, 1.52 to 4.75), altered fetoplacental circulation (OR, 1.56; 95% CI, 1.07 to 2.28), and increased placental thickness and placental venous lakes (OR, 1.85; 95% CI, 1.25 to 2.72).
Conclusion
According to this meta-analysis, pregnant women infected with SARS-CoV-2 are more likely to experience altered Doppler ultrasonography parameters and placental abnormalities, including increased placental thickness, placental venous lakes, altered fetoplacental circulation, and cerebroplacental ratio. However, the limited number of case-control studies requires larger sample sizes to validate and enhance the evidence.
6.Analysis of the Characteristics of Female Herbal Extract Therapy of Professor Zhu Kangmei,One of the Representative Inheritors of"Shanghai-style Herbal Extract Culture"
Lanying HUANG ; Kangmei ZHU ; Xiaotian ZHANG ; Qi CHEN
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(8):2095-2100
Herbal extract,also known as"ointment",is one of the traditional Chinese medicine's dosage forms,which has tonic and therapeutic effects.Traditional Chinese medicine has its own characteristics in the treatment and recuperation of female diseases.According to statistics,women,as a special group,occupy the vast majority of people taking herbal extract.This paper extracted the unique understanding about the special physiological and pathological characteristics of women of Professor Zhu Kangmei,a famous traditional Chinese physician in Shanghai and one of the representative inheritors of"Shanghai-style herbal extract culture".And the characteristics of Professor Zhu's herbal extract for women's sub-health and disease states are analyzed.Her characteristics of the herbal extract in the treatment of women with various prone diseases such as primary amenorrhea,functional uterine bleeding,uterine fibroids and climacteric syndrome are enumerated respectively.Professor Zhu's typical medical records of the herbal extract for the treatment of women's multiple diseases are also listed and analyzed.
7.Distribution and significance of CD1a+and CD83+dendritic cells in lung tissue of COPD mice
Lanying ZHANG ; Fuan ZHANG ; Maomao LIU ; Jie CHEN ; Jian ZHOU ; Yuting LIU ; Yao OUYANG
Tianjin Medical Journal 2024;52(9):913-916
Objective To study the distribution and significance of CD1a and CD83 positive dendritic cells(DCs)in lung tissue of chronic obstructive pulmonary disease(COPD)mice.Methods Twenty C57BL/6 mice were randomly divided into the air control group and the smoked COPD group(n=10 for each group).COPD mouse model was established using cigarette smoking method.Mice were executed within 24 h after the last cigarette smoking,and right lower lung was collected.Body mass changes and lung histopathological changes of mice were observed in two groups.Mean linear intercept(MLI)was measured,and expression levels of CD1a+and CD83+DCs in lung tissue were detected by immunohistochemistry.Results The body mass of mice at 7,14,21 and 28 d after modeling was lower in the smoked COPD group than that in the air control group(P<0.05).HE staining showed that the normal alveolar structure of lung tissue of mice in the smoked group was disrupted,with multiple alveoli fused with each other to form a larger alveolar lumen,a large number of inflammatory cells infiltrated in alveolar intervals,and walls of the alveoli were thickened.COPD modeling was successful.Compared with the air control group,MLI values(μm)increased in the smoked COPD group(28.30±3.47 vs.50.40±3.60),and the number of CD1a+DCs(per field of view)in lung tissue increased(9.58±2.18 vs.17.08±3.67),while the number of CD83+DCs(per field of view)decreased(19.78±4.95 vs.8.02±3.30)(all P<0.05).Conclusion The number of CD1a+DCs in lung tissue is increased and the number of CD83+DCs in lung tissue is decreased in the smoked COPD group of mice,and cigarette smoking may have impaired DC maturation.
8.Early pregnancy fasting plasma glucose levels based on pre-pregnancy body mass index as a predictor of gestational diabetes mellitus
Lanying WANG ; Yao SHI ; Zhoufen MAO ; En YANG ; Guili CHEN ; Jianting MA
Chinese Journal of Perinatal Medicine 2024;27(5):371-378
Objective:To investigate the value and clinical significance of fasting plasma glucose (FPG) in early pregnancy (8-12 gestational weeks) as a predictor of gestational diabetes mellitus (GDM) among women with different pre-pregnancy body mass index (pre-BMI) categories.Methods:A retrospective study was conducted including 9 710 singleton pregnant women (FPG levels in early pregnancy ≤5.6 mmol/L) who underwent prenatal screening and delivery in Yuyao People's Hospital from January 2020 to December 2022. Participants were stratified based on their pre-BMI as follows: <18.5 ( n=1 406), ≥18.5 to <25.0 ( n=7 162), ≥25.0 to <30.0 ( n=978), and ≥30.0 kg/m 2 ( n=164). Within each pre-BMI category, women were further divided into four groups based on FPG levels in early pregnancy (<4.5, ≥4.5 to <4.8, ≥4.8 to <5.1, and ≥5.1 mmol/L). Univariate and multivariate logistic regression analysis were used to identify risk factors for GDM, and receiver operating characteristic (ROC) curve was applied to evaluate the efficacy of FPG in early pregnancy based on different pre-BMI in predicting GDM. Results:The overall incidence of GDM in the singleton pregnancy women with FPG levels in early pregnancy ≤5.6 mmol/L was 12.3% (1 197/9 710). For a pre-BMI of <18.5 kg/m 2, the ORs with 95% CIs for GDM within the different FPG categories (<4.5, ≥4.5 to <4.8, ≥4.8 to <5.1, and ≥5.1 mmol/L) were 0.041 (95% CI: 0.015-0.409), 1.834 (95% CI: 1.089-3.088), 6.779 (95% CI: 4.041-11.371), and 13.723 (95% CI: 5.560-33.871), respectively. For pre-BMI of ≥18.5 to <25.0 kg/m 2, the respective the ORs with 95% CIs were 0.048 (95% CI: 0.012-0.203), 2.573 (95% CI: 2.091-3.168), 9.023 (95% CI: 7.240-11.245), and 9.158 (95% CI: 6.484-12.937). For pre-BMI of ≥25.0 to <30.0 kg/m 2, the ORs with 95% CIs were 0.108 (95% CI: 0.053-0.446), 1.698 (95% CI: 1.064-2.654), 7.537 (95% CI: 5.285-13.080), and 9.994 (95% CI: 5.613-18.218). For pre-BMI of ≥30.0 kg/m 2, the ORs with 95% CIs were 0.098 (95% CI: 0.072-1.015), 2.888 (95% CI: 0.911-9.157), 13.674 (95% CI: 3.480-53.736), and 20.509 (95% CI: 6.674-63.019). The optimal cutoff value of FPG in early pregnancy for GDM prediction was 4.7 mmol/L with an area under the curve of 0.752, the risk of GDM significantly increased with FPG levels ≥4.7 mmol/L in early pregnancy across all pregnant women ( OR=17.356, 95% CI: 13.757-21.896, P<0.001). Conclusions:In the singleton pregnancy women with FPG levels in early pregnancy ≤5.6 mmol/L, FPG in early pregnancy is an independent risk factor for the occurrence of GDM; for pregnant women stratified by the same pre-BMI, the risk of developing GDM increases progressively with the rise of FPG in early pregnancy. FPG in early pregnancy has a certain value in predicting the occurrence of GDM.
9.Evaluation of the effect of SARS-CoV-2 infection on Doppler ultrasound and placental findings of pregnant women: a systematic review and meta-analysis
Lanying CHEN ; Tingting YIN ; Danni CAI ; Xiaomin CHEN
Ultrasonography 2024;43(6):424-437
Purpose:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect the human placenta and has been shown to have an adverse effect on Doppler ultrasound parameters and placental features. However, the specific effects of the SAS-CoV-2 infection on the fetal-placental unit in pregnant women remain unclear. The aim of this systematic review and meta-analysis was to evaluate the impact of SARS-CoV-2 infection on Doppler ultrasound and placental findings in pregnant women.
Methods:
A systematic search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. Odds ratios (ORs) were calculated, along with their 95% confidence intervals (CIs). Heterogeneity was assessed using Cochrane Q and I2 statistics and the appropriate P-value. The analysis used RevMan 5.3.
Results:
This meta-analysis included 1,210 pregnant women from 10 case-control studies. SARS-CoV-2–infected pregnant women exhibited higher likelihoods of placental abnormalities (OR, 2.62; 95% CI, 1.66 to 4.13), aberrant Doppler values (OR, 1.95; 95% CI, 1.16 to 3.27), an abnormal cerebroplacental ratio (OR, 2.68; 95% CI, 1.52 to 4.75), altered fetoplacental circulation (OR, 1.56; 95% CI, 1.07 to 2.28), and increased placental thickness and placental venous lakes (OR, 1.85; 95% CI, 1.25 to 2.72).
Conclusion
According to this meta-analysis, pregnant women infected with SARS-CoV-2 are more likely to experience altered Doppler ultrasonography parameters and placental abnormalities, including increased placental thickness, placental venous lakes, altered fetoplacental circulation, and cerebroplacental ratio. However, the limited number of case-control studies requires larger sample sizes to validate and enhance the evidence.
10.Evaluation of the effect of SARS-CoV-2 infection on Doppler ultrasound and placental findings of pregnant women: a systematic review and meta-analysis
Lanying CHEN ; Tingting YIN ; Danni CAI ; Xiaomin CHEN
Ultrasonography 2024;43(6):424-437
Purpose:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect the human placenta and has been shown to have an adverse effect on Doppler ultrasound parameters and placental features. However, the specific effects of the SAS-CoV-2 infection on the fetal-placental unit in pregnant women remain unclear. The aim of this systematic review and meta-analysis was to evaluate the impact of SARS-CoV-2 infection on Doppler ultrasound and placental findings in pregnant women.
Methods:
A systematic search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. Odds ratios (ORs) were calculated, along with their 95% confidence intervals (CIs). Heterogeneity was assessed using Cochrane Q and I2 statistics and the appropriate P-value. The analysis used RevMan 5.3.
Results:
This meta-analysis included 1,210 pregnant women from 10 case-control studies. SARS-CoV-2–infected pregnant women exhibited higher likelihoods of placental abnormalities (OR, 2.62; 95% CI, 1.66 to 4.13), aberrant Doppler values (OR, 1.95; 95% CI, 1.16 to 3.27), an abnormal cerebroplacental ratio (OR, 2.68; 95% CI, 1.52 to 4.75), altered fetoplacental circulation (OR, 1.56; 95% CI, 1.07 to 2.28), and increased placental thickness and placental venous lakes (OR, 1.85; 95% CI, 1.25 to 2.72).
Conclusion
According to this meta-analysis, pregnant women infected with SARS-CoV-2 are more likely to experience altered Doppler ultrasonography parameters and placental abnormalities, including increased placental thickness, placental venous lakes, altered fetoplacental circulation, and cerebroplacental ratio. However, the limited number of case-control studies requires larger sample sizes to validate and enhance the evidence.

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